Document Detail

Cell cycle-dependent expression of cyclooxygenase-2 in human fibroblasts.
MedLine Citation:
PMID:  11156939     Owner:  NLM     Status:  MEDLINE    
The purpose of this investigation is to determine whether the levels of cyclooxygenase-2 (COX-2) expression are cell cycle dependent. We used a serum-starved human foreskin fibroblast model to determine changes in COX-2 mRNA, protein, and promoter activity in response to stimulation with interleukin-1b (IL-1b) and phorbol 12-myristate 13-acetate (PMA) at G0, G1, S and G2/M phases of the cell cycle. IL-1b (1 ng/ml) and PMA (100 nM) induced robust COX-2 expression in the G0 cells, and the level of COX-2 expression declined progressively after the cells had entered the cell cycle. The COX-2 mRNA level at G1, S and G2/M phases of the cell cycle was 76%, 46%, and 30% of that at G0, respectively. A 5-flanking promoter fragment of COX-2 constructed into a luciferase expression vector was transfected into cells. The promoter activity in response to PMA stimulation was significantly higher in G0 than in S phase cells. These results imply that G0 cells are the key players in inflammation and other COX-2-dependent pathophysiological processes. When the cells are in the proliferative phase, COX-2 inducibility becomes restrained probably by an endogenous control mechanism to avoid COX-2 mediated oxidative DNA damage.
D W Gilroy; M A Saunders; L Sansores-Garcia; N Matijevic-Aleksic; K K Wu
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Publication Detail:
Type:  Journal Article     Date:  2000-12-08
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  15     ISSN:  0892-6638     ISO Abbreviation:  FASEB J.     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-02-22     Completed Date:  2001-03-22     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  288-90     Citation Subset:  IM    
Vascular Biology Research Center and Division of Hematology, Department of Medicine, University of Texas-Houston Medical School, Houston, Texas 77030-1503, USA.
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MeSH Terms
Cell Cycle / physiology*
Cells, Cultured
Cyclooxygenase 2
Fibroblasts / cytology*,  enzymology*
G0 Phase
Gene Expression Regulation, Enzymologic / drug effects,  physiology*
Isoenzymes / genetics*,  metabolism
Membrane Proteins
Models, Biological
Promoter Regions, Genetic / drug effects
Prostaglandin-Endoperoxide Synthases / genetics*,  metabolism
S Phase
Skin / cytology
Tetradecanoylphorbol Acetate / pharmacology
Reg. No./Substance:
0/Isoenzymes; 0/Membrane Proteins; 16561-29-8/Tetradecanoylphorbol Acetate; EC 2; EC protein, human; EC Synthases

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